Excitatory neurotransmission in the brain is mediated mainly via ionotropic glutamate receptors. These receptors are anchored at the postsynaptic membrane by cytoplasmic proteins concentrated in the postsynaptic density (PSD). PSD proteins may help to shape the postsynaptic response to glutamate, but even after the full range of possible biochemical and electrophysiological effects of these molecules has been documented in vitro, their actions in vivo will depend on how they are physically arranged and organized at the synapse. Modern biochemical techniques permit construction of a topological diagram of protein-protein interactions within the macromolecular complex of the PSD, but provide no direct information on the positioning of the elements of this complex, the "supramolecular architecture" of these molecules. The present research will harness new tools for ultrastructural localization of proteins to investigate the supramolecular architecture of the PSD, as a step toward elucidation of the structure and function of the excitatory synapse.